Corrigendum to "Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity" [Heliyon 8 (10) (October 2022) Article e10798].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10798.].

Protective effects of chlorogenic acid against ionizing radiation-induced testicular toxicity.

Background: Testicular tissues could damage by ionizing radiation (IR) during the treatment of pelvic cancers. The aim of this study was to investigate both the protective and therapeutic effects of chlorogenic acid (CGA) on IR-induced mouse testis tissue damage. Methods: In this experimental study, 70 mice were divided into 3 groups, including group 1 (normal saline), group 2 (IR + normal saline), and group 3 (IR + 5, 10, 20, 40, and 80 mg/kg) CGA via I.P injection. Animals in groups 2 and 3 received a dose of 2.0 Gy total-body irradiation in a single fraction. At two determined time points (16 h and 35 days after exposure), the testis and caudal part of both epididymis were isolated and underwent subsequent analyses. Results: The results showed that irradiation of mice caused massive damage to spermatogenesis, seminiferous tubules, basal lamina, Leydig cells, and sperm parameters. Further biochemical assessment of the data demonstrated that 40 mg/kg CGA almost restored MDA to a normal level. In addition, the level of SOD, TAC, and GSH were significantly increased in the 40 mg/kg CGA treated group. Molecular evidence confirmed the protective effects of CGA and also revealed that the ratio of Bax/Bcl-2 in the presence of 40 mg/kg CGA was significantly decreased compared to IR and some treated groups. Conclusion: The protective and therapeutic effects of CGA on testis were found to be positively correlated with the dose level.

Chlorogenic acid improves functional potential of follicles in mouse whole ovarian tissues in vitro.

BACKGROUND: Chlorogenic acid (CGA) is one of the well-known polyphenol compounds possessing several important biological and therapeutic functions. In order to optimize a culture system to achieve complete development of follicles, we focused on the effects of CGA supplementation during in vitro culture (IVC) on follicular development, oxidative stress, antioxidant capacity, developmental gene expression, and functional potential in cultured mouse ovarian tissue. METHODS AND RESULTS: The collected whole murine ovaries were randomly divided into four groups: (1) non-cultured group (control 1) with 7-day-old mouse ovaries, (2) non-cultured group (control 2) with 14-day-old mouse ovaries, (3) cultured group (experimental 1) with the culture plates containing only the basic culture medium, (4) cultured group (experimental 2) with the culture plates containing basic culture medium + CGA (50, 100 and 200 µmol/L CGA). Afterward, histological evaluation, biochemical analyses, the expression assessment of genes related to follicular development and apoptosis as well as the analysis of 17-ß-estradiol were performed. The results showed that supplementation of ovarian tissue with the basic culture media using CGA (100 µmol/l) significantly increased the survival, developmental and functional potential of follicles in whole mouse ovarian tissues after 7 days of culture. Furthermore, CGA (100 µmol/L) attenuated oxidative damage and enhanced the concentration of antioxidant capacity along with developmental gene expression. CONCLUSION: It seems that supplementation of ovarian tissue with culture media using CGA could optimize follicular growth and development in the culture system.

Post-treatment with metformin improves random skin flap survival through promoting angiogenesis in rats.

Skin flap necrosis has been remained as an unsolved problem in plastic and reconstructive surgeries. Here, we explored the effects of metformin post-treatment on random skin flap survival in rats. An 8.00 × 2.00 cm dorsal skin flap was created in 24 rats and they were then divided into three groups (n = 8) including Control, metformin (Met) 50.00 mg kg-1 and Met 100 mg kg-1. All animals were administrated orally until seven days after flap surgery. Flap survival, the number of blood vessels and mast cells in the flap tissues were analyzed. Vascular endothelial growth factor (VEGF) expression levels in flap tissues was also determined using immunohistochemical methods. The percentage of survival area in Met 50.00 mg kg-1 and Met 100 mg kg-1 groups were significantly higher compared to control. The blood vessel density and the VEGF positive cells in the viable areas of flaps showed a significant increase in Met 50.00 mg kg-1 group compared to control group. The results of this study suggested that treatment with metformin, especially with low dose following skin flap surgery was effective in improving the flap survival and increasing the neovascularization in the flaps tissues of rats.

Effect of chlorogenic acid on follicular development, hormonal status and biomarkers of oxidative stress in rats with polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder. Chlorogenic acid (CGA) bears antioxidant properties with protective effects on different tissues. This study was conducted to evaluate the effect of CGA on follicular development, hormonal status and biomarkers of oxidative stress in a rat model of PCOS. In this experimental study, 18 rats were divided into three equal groups including: control, non-treated PCOS [(estradiol valerate (EV): 40.00 mg kg-1 intramuscularly)], and PCOS-CGA (EV: 40.00 mg kg-1 intramuscularly and CGA: 100 mg kg-1 intraperitoneally once a week for eight consecutive weeks). At the end of treatment period, all rats were anesthetized. Then 5.00 mL blood samples of rats in the three groups were taken and prepared for hormonal analyses and their ovaries were isolated and dissected mechanically free of fat and mesentery. The ovaries underwent the following analyses: Morphological study with Hematoxylin and Eosin staining and biochemical study using the malondialdehyde (MDA) level and total antioxidant activity. Data were analyzed using one-way ANOVA and post hoc Tukey's test. The serum level of luteinizing hormone, estrogen, testosterone, antioxidant capacity, glutathione and the number of cystic follicles in the PCOS group treated with 100 mg kg-1 Chlorogenic acid compared to the non-treated PCOS group were significantly decreased, however, the serum level of follicle stimulating hormone, progesterone, MDA and the number of secondary, graafian follicles and corpus luteum were significantly increased. Chlorogenic acid could be effective in ameliorating follicular development as well as hormonal and biochemical disorders in rats with PCOS.

Detrimental effects of cerium oxide nanoparticles on testis, sperm parameters quality, and in vitro fertilization in mice: An experimental study.

BACKGROUND: Cerium oxide nanoparticles (CeO 2 NPs) as an important nanomaterial have a wide range of applications in many fields and human beings' exposure to this nanomaterial is unavoidable. The effects of CeO 2 NPs on the male reproductive system are controversial. OBJECTIVE: To determine the effects of the administration of CeO 2 NPs on the testis tissue, sperm parameters, and in vitro fertilization (IVF) in mice. MATERIALS AND METHODS: Twenty-four male mice were divided into three groups (n = 8/each): one control and two experimental groups receiving CeO 2 NPs at doses of 50 and 100 mg/kg body weight, respectively, for 35 days. At the end of the experiment, the diameter of seminiferous tubules (SNTs), epithelial height of SNTs, spermiogenesis index in testes, sperm parameters (count, motility, viability, and morphology), sperm chromatin condensation, DNA integrity, and IVF assays were analyzed. RESULTS: Histological results showed that the tubular diameter, the epithelial height of the SNTs, and the spermiogenesis index were significantly decreased in the experimental groups receiving CeO 2 NPs. All sperm parameters in the experimental groups were significantly reduced and, additionally, the percentages of immature sperms and sperms with DNA damage were significantly increased in groups treated with CeO 2 NPs compared to the control. Furthermore, the rates of IVF and in vitro embryo development were decreased. CONCLUSION: Collectively, the current study showed that oral administration of CeO 2 NPs in mice had detrimental effects on the male reproductive system through inducing testicular tissue alterations, decreasing sperm parameters quality, and also diminishing the IVF rate and in vitro embryonic development.

Developmental Toxicity of the Neural Tube Induced by Titanium Dioxide Nanoparticles in Mouse Embryos.

BACKGROUND: This study investigated the potential effects of Titanium dioxide nanoparticles (Tio2NPs) followed by maternal gavage on fetal development and neural tube formation during pregnancy in mice. METHODS: Thirty pregnant mice were randomly divided into five main study groups including the untreated control and 4 experimental groups (n=6 per group). The control group was treated with normal saline and the experimental groups were orally treated with doses of 30, 150, 300, and 500 mg/kg Body Weight (BW) of Tio2NPs during pregnancy. On gestational day 16 and 19 (n=3 per group), pregnant mice were euthanized and then examined for neural tube defects and compared with control. Serial transverse sections were prepared in both cranial region and in lumbar region of spinal cord. RESULTS: Treatment with Tio2NPs resulted in low fetal weight and short length, dilation of lateral ventricle, thinning of cerebral cortex and spinal cord, spina bifida occulta and an increase in the number of apoptotic neurons in exposed embryos at doses of 300 and 500 mg/kg (p<0.05). CONCLUSION: It seems that exposure to nanoparticles of Tio2 during pregnancy induces growth retardation and for the first time, teratogenicity of this nanomaterial in neural tube development and induction of defects such as spinal bifida, reduction in cortical thickness and dilatation of lateral ventricles were verified which can be related to incidence of apoptosis in central nervous system.

The Effect of Propolis-Gum Arabic as a Novel Nerve Guidance Channel on Regeneration of Sciatic Nerve in Male Rats.

AIM: To investigate the effect of Propolis-gum Arabic as a nerve guidance channel. MATERIAL AND METHODS: Male rats (n=24) were randomly divided into sham surgery, autograft, and Propolis+gum Arabic groups with equal numbers. Under anesthesia, the sciatic nerve was removed, and the gap between the two ending was repaired by Propolis-gum Arabic or nerve autograft. Nerve regeneration was evaluated by sciatic function index (SFI), withdrawal reflex latency (WRL), muscle fiber diameter, number of myelinated axons, myelinated fiber diameter, and immunohistochemical analysis. RESULTS: At 30, 49, 60 and 90 days after surgery, the mean of SFI in Propolis + gum Arabic group was significantly greater than the autograft group (p < 0.03). The mean muscle fiber diameters (30 and 90 days after surgery) and the mean number of myelinated axons (90 days after surgery) in Propolis + gum Arabic group were significantly greater than autograft group (p < 0.05). In addition, 90 days after surgery, the mean myelinated fiber diameter in Propolis + gum Arabic group was significantly higher than autograft group (p < 0.05). CONCLUSION: The results of this study suggest that as guidance channel, the Propolis + gum Arabic may be useful in peripheral nerve regeneration.

Effect of silymarin and metformin on the sperm parameters and histopathological changes of testes in diabetic rats: An experimental study.

BACKGROUND: Oxidative stress is a major contributor to diabetes, which can lead to testicular damage and infertility. OBJECTIVE: This study aimed to compare the effects of metformin as a chemical drug with silymarin as an herbal agent on the sperm parameters and histopathological changes of testes in diabetic rats. MATERIALS AND METHODS: Thirty-two male Wistar rats (250-270 gr) were randomly divided into four groups: 1) control; 2) diabetic; 3) diabetic+metformin 200 mg/kg; and 4) diabetic+silymarin 100 mg/kg. Daily injections were administered intraperitoneally for 56 days. At the end of the treatment, blood sampling was performed for biochemical assessment. Then, the rats were sacrificed and their left testis and epididymis were cut for sperm analysis as well as histopathology and morphometric evaluation. RESULTS: Diabetes was associated with a reduced sperm count, motility, viability, maturity, and chromatin quality of sperm (p ≤ 0.001). It was also associated with a higher malondialdehide level and lower total antioxidant capacity level of serum in comparison with the control group (p ≤ 0.001). There was a significant difference in the seminiferous tubule diameter, germinal epithelium height, and testicular histopathological alterations in the diabetic rats compared with the control rats (p ≤ 0.001). Treatment with metformin and silymarin improved the above-mentioned parameters and this improvement was more substantial in silymarin-treated animals (p ≤ 0.001). CONCLUSION: In diabetic rats, metformin and silymarin improved sperm parameters, sperm DNA integrity, seminiferous tubule diameter, germinal epithelium thickness, and testicular histopathological complications; this improvement was more substantial in the silymarin-treated group. So, the findings of this study suggest that silymarin is more effective than metformin in treating diabetic-induced infertility.

Neurological effects of long-term exposure to low doses of pesticides mixtures in male rats: Biochemical, histological, and neurobehavioral evaluations.

Humans are usually exposed to multiple pesticides in real life, but little is known as yet about the safety of low-dose pesticides mixtures. This study was conducted to evaluate the effects of long-term exposure to very low doses of pesticide mixtures on biochemical, histological, and neurobehavioral alterations in the rat model. For 90 days, four groups of male Wistar rats were given a mixture of five pesticides (in drinking water) in doses of 0, 0.25, 1 and 5 times the legally permitted levels (mg/kg body weight/day). After three-month exposure, the neurobehavioral effects of pesticide mixtures were evaluated by the Morris water maze, elevated plus maze and the open field tests. Then the biochemical and histopathological alterations in the hippocampus of studied animals were evaluated. Results showed that long-term exposure to a combination of five pesticides affected the nervous system in dose-dependent manner. As expected, nearly all of the parameters determined in this study were adversely changed in the high dose group. Exposure to medium dose (permitted level of pesticides mixture) was also able to induce oxidative stress and impaired memory and learning ability, although not all parameters were significantly changed in this group. It means that pesticides may behave differently when mixed. Interestingly, the administration of low doses of these chemicals induced an adaptive response by stimulating the redox system. In conclusion, it seems that the prolonged exposure to pesticide mixtures may cause adverse neurobehavioral effects, even at permitted levels.

The ameliorating effects of Vitamin E on hepatotoxicity of ecstasy.

BACKGROUND: The production of stress oxidative condition in body which is caused by consumption of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) leads to a liver damage. As an antioxidant, Vitamin E can protect cells and tissues against the deleterious effects of free radicals. This study evaluates the protective effects of Vitamin E on MDMA induced liver toxicity. MATERIALS AND METHODS: Twenty-eight male albino mice were randomly assigned to four equal groups. Group 1 received saline (control), Group 2 received MDMA and saline, Group 3 received MDMA, and Vitamin E and Group 4 received Vitamin E. MDMA was injected with single daily dose, three sequential days/week for 5 weeks. At the end of the period, blood samples were collected for a biochemical analysis and then the mice were sacrificed by cervical dislocation for histopathological and biochemical examinations of liver. RESULTS: The administration of Vitamin E attenuated the increased levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase enzymes in serum. Vitamin E treatments significantly restored endogenous antioxidant enzymes (reduced glutathione and superoxide dismutase enzyme) activities as compared with MDMA-treated animals. Histological examination of liver revealed significant morphological tissue injuries in hepatocytes after MDMA being used, but in coadministration of vitamin E and MDMA, these morphological alterations reduced. CONCLUSION: The study showed that MDMA administration has adverse effects on the liver. Vitamin E lessened the deleterious impact considerably.

The effects of exposure to fluoxetine during lactation on testicular tissue and sperm parameters in mice offspring.

Fluoxetine is a selective serotonin reuptake inhibitor is commonly prescribed to treat maternal depression in pregnancy and lactation. This study aimed to investigate the effects of maternal exposure to fluoxetine via lactation on testicular tissue, sperm parameters including count, motility, viability, and normal morphology and testicular oxidative stress status in male mice offspring. Ten mice dams were divided into control and experimental groups. The control group received water and the experimental group received fluoxetine (20.00 mg kg-1) by gavage daily from postnatal days of 0-21. Histology of testis, sperm parameters and oxidative stress in the testicular tissue were analyzed at 80 days after birth in their male offspring (n = 8). Significant reductions in the body and testes weights were observed in animals exposed to fluoxetine. Additionally, fluoxetine exposure significantly reduced all sperm parameters, tubular diameter and epithelial height of the seminiferous tubules as well as Leydig cells number. Significant increases in the testicular malondialdehyde levels and percentage of sperm with chromatin/DNA damage were observed in mice exposed to fluoxetine compared to control. These findings suggest that maternal exposure to fluoxetine during lactation in mice has a negative effect on the testicular tissue of their offspring and impairs the spermatogenesis process which in turn can induce infertility.

Effects of oral administration of titanium dioxide particles on sperm parameters and in vitro fertilization potential in mice: A comparison between nano- and fine-sized particles.

Titanium dioxide particles (TiO2) as the second most widely used materials in consumer products are composed of nano-sized (<100 nm) particles (NPs) and fine-sized (>100 nm) particles (FPs). Toxicological studies on animals have shown that TiO2 NPs exposure can cross the blood-testis barrier and accumulate in the testis resulting in testicular tissue damage and reduction of sperm count and motility. However, there is no information on the toxic effects of TiO2 FPs on male reproductive fertility. Twenty-four adult male mice were randomly divided into three groups including control, TiO2 NPs, and TiO2 FPs (150 mg kg-1 per day). After intragastric administration for 35 days, testicular tissue alterations (seminiferous tubule diameter and germinal epithelial height), sperm parameters (count, motility, viability, morphology, and DNA quality), in vitro fertilization potential, oxidative stress assays such as malondialdehyde (MDA) content, level of glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in testicular tissue were investigated. The results showed that both sizes of TiO2 caused pathologic changes in the testis and significantly increased MDA level and decreased GSH levels and activities of SOD and GPx in testicular tissue. Moreover, the administration of both sizes of TiO2 significantly decreased all of the sperm parameters and in vitro fertility (fertilization rate and pre-implantation embryos development) compared to control. Administration of TiO2 FPs similar to TiO2 NPs through inducing damages to testis led to a marked reduction in sperm quality, in vitro fertilization, and embryos development in male mice.

Protective effects of orally administered thymol against titanium dioxide nanoparticle-induced testicular damage.

In this study, we investigated the potential of thymol and its mode of action to protect against the titanium dioxide (TiO2) nanoparticle-induced testicular damage. Twenty-four rats were randomly divided into four groups: control group, TiO2 (100 mg/kg BW/day) group, TiO2 + thymol (10 mg/kg BW/day) group, and TiO2 + thymol (30 mg/kg BW/day) group. With the exception of the control group, all animals received orally TiO2 nanoparticles for 60 days. In treatment groups, animals were given orally thymol 1 h before TiO2 nanoparticles. Epididymal sperm parameters, testicular histopathology, and spermatogenesis assessments were performed for evaluation of the TiO2 and thymol effects on the testis. Furthermore, antioxidative enzyme activities such as catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA), glutathione (GSH) levels and ferric-reducing antioxidant power (FRAP) value were measured. Intragastric administration of TiO2 for 60 consecutive days caused a significant decrease in sperm quality, widespread histopathological alteration, and significantly induced oxidative stress as manifested by elevated MDA levels and a remarkable decline in antioxidant enzyme activities such as CAT, SOD, and GPx, and also FRAP and GSH levels in testis tissue. Nearly all of these alterations were significantly ameliorated in the groups that orally received thymol before TiO2 nanoparticles administration. The results of this study demonstrated that thymol improved the spermatogenesis defects induced by TiO2 nanoparticles in rats in a dose-dependent manner by protecting the testes against the testicular toxicity. Reduction in TiO2 nanoparticle-induced oxidative stress may have a major role in this protective effect.

Crocetin promotes angiogenesis in human endothelial cells through PI3K-Akt-eNOS signaling pathway.

Previous studies proved the pro-angiogenic effect of Crocetin, a natural carotenoid dicarboxylic acid, in both in vivo and in vitro models. However, the exact mechanism of Crocetin action has not completely been elucidated yet. The current experiment was designed to find the activity of PI3K-Akt-eNOS axis after the treatment of endothelial cells with Crocetin in vitro. Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with various concentrations of Crocetin (1, 5, 25, 50, and 100 µM) over a period of 72 h. Crocetin significantly increased HUVECs viability after 72 h as compared with the control group. We also found that Crocetin promoted the formation of the capillary-like structure compared to the control (p<0.05). Moreover, an improved migration rate and increased MMP-9 activity were observed in HUVECs that received 50 µM Crocetin (p<0.05). Crocetin enhanced the uptake of Ac-LDL which is correlated with increased lipid metabolism. Based on the data from the current experiment, protein level of VEGFR-1, -2 and p-Akt/Akt, p-eNOS/eNOS ratios were increased 72 h after the treatment of HUVECs with Crocetin (p<0.05). In contrast, the transcription level of VEGF was reduced in Crocetin-treated cells. These data demonstrated that Crocetin promotes HUVECs angiogenesis potential by the modulation of VEGF signaling pathway and increased cell viability. The PI3K/Akt/eNOS axis is required for a Crocetin-associated activity in endothelial cells.

Protective Effect of Contralateral, Ipsilateral, and Bilateral Remote Ischemic Preconditioning on Spinal Cord Ischemia Reperfusion Injury in Rats.

AIM: To evaluate the effect of different remote ischemic preconditioning (RIPC) methods in spinal cord ischemia-reperfusion (IR) injury. MATERIAL AND METHODS: A total of 36 rats were distributed to the 6 groups: sham surgery, control (only spinal cord IR), unilateral (hind limb RIPC before spinal cord IR), bilateral (hind limbs RIPC before spinal cord IR), ipsilateral (hind and fore limbs RIPC to the right before spinal cord IR), contralateral (right hind limb and left fore limb as RIPC before spinal cord IR). Thirty minutes after RIPC, the spinal cord was subjected to ischemia for 60 minutes. Seventy two hours after IR, all rats were evaluated by neurological function, histological and biochemical examinations. RESULTS: The mean Motor Deficit Index (MDI) scores in the ipsilateral, contralateral, and bilateral groups were lower than that of the unilateral group (p < 0.05). The mean malondialdehyde (MDA) in ipsilateral group was lower than were control group (p < 0.05). The mean total antioxidant capacity (TAC) and the mean number of normal motor neurons in the experimental groups were significantly higher than increased control group (p < 0.05). The mean plasma levels of catalase in the contralateral, ipsilateral, and bilateral groups were significantly increased compared to control group (p < 0.05). The mean scores of white matter damage in contralateral, bilateral, and unilateral groups were lower than control group (p < 0.05). CONCLUSION: The results of this study show that contralateral, ipsilateral, and bilateral limb RIPC may reduce the complications of spinal cord ischemic injury.

Protective effect of lutein on spinal cord ischemia-reperfusion injury in rats.

OBJECTIVES: Paraplegia is deterioration in motor or sensory function of the lower limbs that can occur after modification of a thoracoabdominal aortic aneurysm. The purpose of this survey was to determine the protective action of lutein on spinal cord ischemia-reperfusion (I-R) damage. MATERIALS AND METHODS: Thirty-five male rats were distributed into five groups: intact, sham, dimethyl sulfoxide (I-R+DMSO), low dose lutein (I-R+0.2 mg/kg lutein), and high dose lutein (I-R + 0.4 mg/kg lutein). Thirty minutes before surgery, a single dose lutein or DMSO was administered to rats of experimental groups. Next, the abdominal aorta was clamped exactly under the left renal artery and proximal to the abdominal aortic bifurcation for 60 min. All animals were evaluated by neurological function and histological and biochemical examinations at 72 hr after I-R. RESULTS: The mean motor deficit index (MDI) scores in lutein groups were lower compared with the DMSO group (P<0.001). Plasma level of malondialdehyde in lutein groups decreased compared with the DMSO group (P<0.05). Plasma level of total antioxidative capacity was increased in the high lutein group compared with low dose lutein and sham groups (P<0.05). Mean number of normal motor neurons in lutein groups was greater compared with the DMSO group (P<0.001). There was a significant negative correlation between MDI scores and the number of normal neurons (r= -0.764, P<0.001). CONCLUSION: Findings of the present study demonstrate that lutein may support spinal cord neurons from I-R damage.

Priming with oxytocin and relaxin improves cardiac differentiation of adipose tissue-derived stem cells.

Previous studies have identified the heart as a source and a target tissue for oxytocin and relaxin hormones. These hormones play important roles in the regulation of cardiovascular function and repair of ischemic heart injury. In the current study, we examined the impact of oxytocin and relaxin on the development of cardiomyocytes from mesenchymal stem cells. For this purpose, mouse adipose tissue-derived stem cells (ADSCs) were treated with different concentrations of oxytocin or relaxin for 4 days. Three weeks after initiation of cardiac induction, differentiated ADSCs expressed cardiac-specific genes, Gata4, Mef2c, Nkx2.5, Tbx5, α- and ß-Mhc, Mlc2v, Mlc2a and Anp, and cardiac proteins including connexin 43, desmin and α-actinin. 10 -7 M oxytocin and 50 ng/mL relaxin induced the maximum upregulation in the expression of cardiac markers. A combination of oxytocin and relaxin induced cardiomyocyte differentiation more potently than the individual factors. In our experiment, oxytocin-relaxin combination increased the population of cardiac troponin I-expressing cells to 6.84% as compared with 2.36% for the untreated ADSCs, 3.7% for oxytocin treatment and 3.41% for relaxin treatment groups. In summary, the results of this study indicated that oxytocin and relaxin hormones individually and in combination can improve cardiac differentiation of ADSCs, and treatment of the ADSCs and possibly other mesenchymal stem cells with these hormones may enhance their cardiogenic differentiation and survival after transplantation into the ischemic heart tissue.

Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis / Efeitos sinérgicos do extrato aquoso da fruta da jujuba em combinação com administração de Mesalazina (via oral) e Asacol (intracolônico) na melhora de colite ulcerativa em modelo animal

ABSTRACT This study was done to investigate the synergistic impacts hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis (UC). After the induction of UC and with the development of signs, the treatment groups daily received the hydro extract of jujube fruit (200 mg/kg, orally, enema), Mesalazine (30 mg/kg, orally) and Asacol (10 mg/kg, enema). After 10 days, rats were euthanized and were studied. Findings indicated a significant increase in Myeloperoxidase (161.66 ± 10.40), Nitric oxide (216.01 ± 17.55), IL-6 (138.54 ± 7.02), and TNF-α (123.87 ± 9.80) colon tissue levels and pathological damage of positive control group compared with the negative control group. Hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) group represented a higher capability in significantly decreasing Myeloperoxidase (73.33 ± 9.07), Nitric oxide (81.66 ± 10.50), IL-6 (51.69 ± 5.19), TNF-α (30.59 ± 5.50) levels and pathological damage in compared with the other treatment groups. Considering accessibility and affordability of jujube fruit and the side effects of routine drugs, taking a combination of jujube fruit with low doses of routine pharmaceutical drugs can improve and cure ulcerative colitis disease.

RESUMO Este estudo foi realizado para investigar os impactos sinérgicos do extrato aquoso do fruto da jujuba em combinação com a administração de Mesalazina (por via oral) e Asacol (intracolônico) na melhora do modelo animal de colite ulcerativa. Após a indução da colite ulcerativa e com o desenvolvimento de sinais, os grupos de tratamento receberam diariamente o extrato aquoso do fruto da jujuba (200 mg/kg, via oral, enema), Mesalazina (30 mg/kg, via oral) e Asacol (10 mg/kg, enema). Após 10 dias, os ratos foram eutanasiados e estudados. Os achados indicaram um aumento significativo dos níveis de mieloperoxidase (161,66 ± 10,40), óxido nítrico (216,01 ± 17,55), IL-6 (138,54 ± 7,02) e TNF-α (123,87 ± 9,80) no tecido do cólon e dano patológico do grupo controle positivo comparado com o grupo controle negativo. O extrato aquoso da fruta de jujuba em combinação com Mesalazina (oral) e Asacol (intracolônico) representou maior capacidade de redução significativa dos níveis de mieloperoxidase (73,33 ± 9,07), óxido nítrico (81,66 ± 10,50), IL-6 (51,69 ± 5,19), TNF-α (30,59 ± 5,50) e dano patológico em comparação com os outros grupos de tratamento. Considerando a acessibilidade e disponibilidade do fruto da jujuba e dos efeitos colaterais dos medicamentos de rotina, tomar uma combinação de jujuba com baixas doses de medicamentos farmacêuticos de rotina pode melhorar e curar a colite ulcerativa.